Nonoperative management of biliopleural fistula following living‐donor liver transplantation: A case report

Key Clinical Message Biliopleural fistula is a rare but serious complication after liver transplantation that should be managed nonoperatively with antibiotics, pleural drainage, decompression of high‐pressure biliary tract, or ultimately surgery in unresponsive cases. Abstract Bilious pleural effusion is a rare entity often iatrogenic, following hepatobiliary surgeries and biliary interventions, and has been reported only in a limited number of patients after liver transplantation. A 5‐year‐old girl underwent living donor liver transplantation due to progressive familial intrahepatic cholestasis. At the 7th day of the postoperative course, due to increased liver enzymes and bilirubin levels and intrahepatic bile duct dilatation on sonography, Magnetic Resonance Cholangiopancreaticography followed by a liver biopsy were performed; the findings demonstrated moderate intrahepatic bile duct dilatation and moderate cellular rejection associated with mild cholestasis, respectively. The patient was therefore administered a pulse of methylprednisolone; however, due to fever, peritonitis and also sonographic evidence of infected biloma collection adjacent to the transplanted liver, the patient underwent surgery. Laparotomy and peritoneal washout were performed and a Jackson‐Pratt drain was inserted adjacent to the liver cut surface. Succeeding tachypnea on 28th post day, led to detection of right side massive pleural effusion on chest Xray and hence thoracostomy tube was inserted. A diagnosis of biliopleural fistula was established and broad‐spectrum intravenous antibiotic therapy was started, followed by cholangiography, fistula closure, and bile duct stricture ballooning and internal‐external biliary catheter insertion. The patient was discharged in generally good condition on the 50th posttransplant day. The diagnosis of biliopleural fistula is facilitated with the utilization of chest imaging and pleural fluid analysis, however, a high index of suspicion is required.


| INTRODUCTION
Biliopleural fistula (BPF) is a rare condition that presents as pleural effusion and may develop congenital or following liver trauma, inflammatory and neoplastic processes, parasitic infections, or iatrogenic after hepatobiliary procedures. 1 Bile contents can damage the lung and lead to ominous respiratory complications such as pneumonia, empyema, lung caustic injury, adhesion formation around the lung (entrapped lung), and even acute respiratory distress syndrome (ARDS).So, early detection is important in order to treat appropriately.
We describe a case of BPF that developed following living-donor liver transplantation (LDLT) that was managed nonoperatively.Our purpose is to increase the awareness of surgeons and physicians dealing with transplant patients of this rare but serious complication.

| CASE PRESENTATION
A 5-year-old girl known history of progressive familial intrahepatic cholestasis (PFIC), presented with pruritus since 3 years, growth retardation (weight 13 Kg; under 5th percentile of weight for age) and recent abdominal distention.She also had a history of previous abdominal operation 1.5 year ago for exploring biliary system and liver biopsy that no biliary diversion was performed.She referred to our center for liver transplantation and underwent LDLT from her 26 years old mother.A left lateral segment of the donor's liver (single duct, single left hepatic artery and single portal vein) was transplanted and via Roux-en-Y hepaticojejunostomy anastomosis, the only draining duct was anastomosed to the Roux limb of jejunum.During the first postoperative week patient had an acceptable course but due to a cholestatic pattern of increased liver enzymes and bilirubin levels (Table 1), sonography of transplanted liver was done that revealed moderate intrahepatic bile duct dilatation with normal color doppler sonography, so Magnetic Resonance Cholangiopancreatography (MRCP) was performed on the 7th postoperation day, demonstrating moderate intrahepatic bile duct dilatation (Figure 1) but no clay stool was reported during her course.
Due to increased level of serum aminotransferases and bilirubin, liver biopsy was performed that showed moderate cellular rejection associated with mild cholestasis, so pulse of methylprednisolone was added to antibiotic therapy.During the second week after the transplantation, fever and abdominal pain developed and abdominal sonography revealed collection formation adjacent to the transplanted liver, along with the clinical impression of peritonitis, laparotomy was undertaken and a large volume of infected biloma (almost 300 mL) was detected adjacent to the liver cut surface and right subdiaphragmatic area without frank site of bile leakage.The peritoneal cavity was irrigated and a Jackson-Pratt (JP) drain was inserted adjacent to the cut surface and it's daily drainage was subsequently measured and recorded.
Gradually drainage volume shifted toward zero but on the 28th postoperative day, she developed tachypnea without evidence of fever, cough, sputum, or chest pain.Chest X-Ray (CXR) revealed a right-side massive pleural effusion (Figure 2); therefore, a pleural pigtail was inserted under ultrasound (US) guide and 300 mL yellowish turbid (bilious) fluid was aspirated.Pleural fluid analysis revealed high bilirubin levels (pleural fluid total Bilirubin; 8.73, simultaneous serum total Bilirubin; 0.83) with neutrophil dominant leukocytosis (WBC count, 25,000; Neu, 98%) and fluid culture was positive for Escherichia coli.A suspicion of BPF was made and broad-spectrum intravenous antibiotics (Imipenem & Linezolid) were continued.A chest computed tomography (CT) scan was done 3 days after the pigtail drain insertion, which showed less of a right-side pleural effusion with accurate placement of the pigtail (Figure 3).
Daily thoracostomy drain volume was 220 mL initially and declined to 40 mL after 2 weeks while the JP drain output was nil.It was hence deduced that there was some minor bile leakage from either the liver cut surface or the hepaticojejunostomy anastomosis.The mainstay of management of both scenarios is lowering the bile flow pressure, therefore the patient was candidate for cholangiography.Under US guide and conscious sedation after catheterization of dilated bile ducts of segments 2 and 3, Cholangiography was performed which revealed leakage from the allograft cut surface and some passage into the right hemithorax, plus bilioenteric continuity was confirmed with free passage of injected dye to the jejunal limb during cholangiography (Figure 4).Therefore, bile duct ballooning at the level of bilioenteric anastomosis was undertaken, and subsequently, the fistula ostium was closed with a mixture of glue and lipiodol.An internal-external biliary draining catheter was also inserted.Following this procedure, the drainage output of the thoracostomy tube was decreased notably.
The patient was discharged in generally good condition on the 50th posttransplant day with the thoracostomy tube in situ, and a decline in liver function tests (Table 1).On discharge, no intra-abdominal collection was found in the US and the daily drain volume was less than 30 mL.She was followed with weekly visits as an outpatient in clinic.Gradually chest drainage fluid decreased and shifted toward zero in three subsequent weeks and finally the thoracostomy tube was removed following a satisfactory CXR.(Figure 5).

| DISCUSSION
Bilious pleural effusion is a rare entity that tends to be mainly iatrogenic, following hepatobiliary surgeries and biliary interventions, and has been reported only in a limited number of patients following LTx.A brief review of reported cases of BPF and the formation of bilious pleural effusion following hepatobiliary interventions and surgeries are listed in Table 2.
Previously, Karnik et al. reported bilothorax following orthotopic LTx in a 62-year-old male with hepatocellular carcinoma and hepatitis B virus, who presented with a massive right-sided pleural effusion, in which drainage of the pleural fluid along with endoscopic retrograde cholangiopancreatography (ERCP) revealed bile leak at the biliary anastomotic site.The case was managed with biliary stent placement. 26López-Garnica et al. 25 also reported a 44-year-old male patient with nonalcoholic fatty liver disease and cirrhosis due to methotrexate use, who underwent LTx from a deceased donor, presenting with abdominal pain, nausea, and diarrhea 1 month after surgery.The patient was diagnosed with a case of BPF based on pleural effusion drainage consistent with bile fluid characteristics.The patient was managed via ERCP with sphincterotomy and internal plastic stent placement into the biliary tree.However, the patient presented with jaundice 2 months after stent placement due to stenosis and was eventually treated with balloon dilatation and biliary stent replacement.Various theories have been explained as the cause of bilious pleural effusion following LTx, the most probable of which are: • Biliary outflow stricture and obstruction following LTx with high-pressure gradient in the biliary tract results in; • Flowing bile into low-pressure spaces, such as the thoracic cavity with negative pressure, and finally bilious pleural effusion forms 27 and • Subdiaphragmatic collection formation led to inflammation & erosion through the diaphragm and BPF forms. 28 Intraperitoneal fluid has been transmitted via intradiaphragmatic pleuroperitoneal pores and finally bilious pleural effusion forms.
• Undiagnosed intraoperative diaphragmatic injury, which is less probable because of evidence of pneumothorax, results in BPF.
Our case had a history of previous abdominal surgery with a lot of adhesions being encountered during the transplant procedure mostly in the right upper quadrant of the abdomen.As adhesiolysis was done mainly using electrocautery and the argon beam coagulator, this may have resulted in ischemia and micro-damage in less vascularized tendinous part of diaphragm which along with the postoperative intra-abdominal infection may have increased the risk of fistula formation.
Taking into account all of these considerations, no consensus was reached regarding the precise cause of BPF in our case.Overall, although the diagnosis of BPF is facilitated with the utilization of chest imaging and pleural fluid analysis, a high index of suspicion is required.We

F I G U R E 4
Image of the percutaneous transhepatic cholangiography demonstrating dilated intrahepatic bile ducts with stricture at the site of hepaticojejunostomy anastomosis and leakage from cut surface resulting in biliopleural fistula (white arrow).Bilio-enteric continuity was seen with free passage of injected dye to the jejunal limb during cholangiography (black arrow).were able to manage the case based on a nonoperative approach via broad-spectrum intravenous antibiotic therapy, followed by cholangiography, fistula closure, and bile duct stricture ballooning.The mainstay of treatment of BPF is a conservative approach including evacuation of bilious fluid from the pleural cavity (tube thoracostomy), decompression of high-pressure biliary tract (ballooning and stent placement and endoscopic sphincterotomy), percutaneous drainage of intraperitoneal collection, and antibiotic administration while the closure of the fistula (at first nonsurgically, then surgically) remains for patients unresponsive to nonoperative approach. 26,28

| CONCLUSION
We report a pediatric patient with BPF following LDLT who was treated with a multidisciplinary nonoperative approach.BPF is a rare complication of liver transplantation can be associated with considerable respiratory complications.The diagnosis of BPF is facilitated with the utilization of chest imaging and pleural fluid analysis, however a high index of suspicion is required.Use of electrocautery and argon beam coagulator for hemostasis may result in ischemia of hemidiaphragm, and should be considered as an additional hypothetical factor for BPF formation.

F I G U R E 1
Magnetic Resonance Cholangiopancreatography (MRCP) shows moderate intrahepatic bile duct dilatation (green arrow).F I G U R E 2 Chest roentgenogram demonstrating massive right side pleural effusion, due to biliopleural Fistula.

F I G U R E 5
Chest X-ray after thoracostomy tube removal.F I G U R E 3 (Left Image) Axial computed tomographic image in soft tissue window demonstrating limited right side pleural effusion 3 days after thoracostomy drain insertion.(Right Image) Coronal computed tomographic image indicating pigtail drain in the right pleural cavity (black arrow).
Review of reported cases of Biliopleaural fistula and the formation of bilious pleural effusion following hepatobiliary interventions and surgeries.
AbbreviationsT A B L E 2 (Continued)